Ullmann Nicola, Peri Francesca, Florio Olivia, Porcaro Federica, Profeti Elisa, Onofri Alessandro, Cutrera Renato
Pediatric Pulmonology & Respiratory Intermediate Care Unit, Sleep, and Long Term Ventilation Unit, Academic Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
Front Pediatr. 2022 Jul 1;10:920066. doi: 10.3389/fped.2022.920066. eCollection 2022.
There is a growing need for advanced treatment in children with persistent and severe asthma symptoms. As a matter of fact, between 2 and 5% of asthmatic children experience repeated hospitalizations and poor quality of life despite optimized treatment with inhaled glucocorticoid plus a second controller. In this scenario, mepolizumab, a humanized monoclonal antibody, has proven to be effective in controlling eosinophil proliferation by targeting interleukin-5 (IL-5), a key mediator of eosinophil activation pathways. Mepolizumab is approved since 2015 for adults at a monthly dose of 100 mg subcutaneously and it has been approved for patients ≥ 6 years of age in 2019. Especially in children aged 6 to 11 years, mepolizumab showed a greater bioavailability, with comparable pharmacodynamics parameters as in the adult population. The recommended dose of 40 mg every 4 weeks for children aged 6 through 11 years, and 100 mg for patients ≥ 12 years provides appropriate concentration and proved similar therapeutic effects as in the adult study group. A marked reduction in eosinophil counts clinically reflects a significant improvement in asthma control as demonstrated by validated questionnaires, reduction of exacerbation rates, and the number of hospitalizations. Finally, mepolizumab provides a safety and tolerability profile similar to that observed in adults with adverse events mostly of mild or moderate severity. The most common adverse events were headache and injection-site reaction. In conclusion, mepolizumab can be considered a safe and targeted step-up therapy for severe asthma with an eosinophilic phenotype in children and adolescents.
对于患有持续性严重哮喘症状的儿童，对先进治疗的需求日益增长。事实上，尽管使用吸入性糖皮质激素加第二种控制药物进行了优化治疗，但仍有2%至5%的哮喘儿童反复住院且生活质量较差。在这种情况下，美泊利珠单抗，一种人源化单克隆抗体，已被证明可通过靶向白细胞介素-5（IL-5）来有效控制嗜酸性粒细胞增殖，IL-5是嗜酸性粒细胞激活途径的关键介质。美泊利珠单抗自2015年起被批准用于成人，每月皮下注射剂量为100毫克，2019年已被批准用于≥6岁的患者。特别是在6至11岁的儿童中，美泊利珠单抗显示出更高的生物利用度，其药效学参数与成人人群相当。6至11岁儿童每4周推荐剂量为40毫克，≥12岁患者为100毫克，可提供适当的浓度，并证明与成人研究组具有相似的治疗效果。嗜酸性粒细胞计数的显著降低在临床上反映出哮喘控制的显著改善，这通过经过验证的问卷、加重率的降低和住院次数得到证明。最后，美泊利珠单抗的安全性和耐受性与在成人中观察到的相似，不良事件大多为轻度或中度严重程度。最常见的不良事件是头痛和注射部位反应。总之，美泊利珠单抗可被认为是一种安全且有针对性的强化治疗方法，用于治疗儿童和青少年中具有嗜酸性粒细胞表型的重度哮喘。
